Ovarian cancer Sixth commonest cancer worldwide Fifth most frequent cause of cancer death The second most common gynecological cancer, after

endometrial cancer Approximately 1 in 70 newborn girls will develop

ovarian cancer during her lifetime 75% of women present with advanced disease Documented to occur in females of all ages.

Origin of Ovarian Tumors

Ovarian CancerHistologic Distribution

95%

4-5% ۱%

EpithelialGerm CellSex Cord Stroma

Five year survival

Stage Incidence

Ovarian Cancer StagingStage I - Limited to ovaries

A. Unilateral ovaryB. Bilateral ovariesC. Positive cytology

Stage II - Limited to pelvis

A. Extends to uterus or tubesB. other pelvic organs

Stage III – Spread to upper abdomen or regional lymph nodes

A. Microscopic spread and/or Positive retroperitoneal lymph nodes B. Macroscopic < 2 cmC. Macroscopic > 2 cm

Stage IV - Spread outside peritoneum, pleura or parenchymal

Ovarian Cancer Surgical Debulking and Staging

Exploration

Washings/Ascites

(Staging)

TAH/BSO

Biopsies(Staging)

Goals (Debulking)•Assessment of extent of disease

•Optimal tumor reduction

TAH = total abdominal hysterectomyBSO = bilateral salphingo-oophorectomy

What is conservative? To an interventionist it might mean

Traditional Old fashioned Unprogressive

But it also means Careful, Cautious and Preserving Protecting Saving

General PrincipleAny type of new managementwhich could impair the patients survival must not be employed if the “classic” treatments offer sure cure

What is conservative surgery in Ovarian Cancer?

Unilateral salpingo-oophorectomy

Full surgical staging Washings Omentectomy Appendectomy Node biopsies A thorough abdominal exploration and biopsy of any abnormal areas Endometrial biopsy should be performed to exclude endometrial cancer

Do not biopsy the contralateral ovary

Adjuvant chemotherapy?

Simply it should be called Fertility Sparing Surgery (FSS)

Sex cord - stromal tumors Malignant sex cord-stromal neoplasms are rare (1%)

Most commonly observed in postmenopausal period

Malignant neoplasms are generally considered to be low-grade

Disease was confined to the ovary in up to 95% of women

Conservative surgery is possible in a high percentage of young patients

Subsequent pregnancies have been documented only in case reports and small series (Powell et al)

Germ cell tumors Account for only about 5% of all malignant ovarian

neoplasms

Arise primarily in young women between 10 and 30 years of age

Most OGCTs (60%) are stage I at initial presentation

Most patients can be safely treated with Conservative surgery rather than radical one

Highly sensitive to platinum-based chemotherapy

The survival in advanced disease is still over 90%

Literature Review of Reproductive Function Following FSS for Malignant OGCT

Author No. Patients No. Normal menses No. Pregnancies

Greshenson 1988 40 27/40 (68%) 22 in 11

Brewer 1999 16 13/14 (93%) 5 in 3

Low 2000 74 43/47 (92%) 14 in 19

Zanetta 2001 138 80/81 (99%) 41 in 16

Tangir 2003 64 28/40 (69%) 47 in 29

Greshenson 2002 133 59/77 (77%) 37 in 38

Ovarian tumors of low malignant potential

Account for 10–15% of all epithelial tumors

Good prognosis, with a 10-year survival of approximately 90%

The median age is 15–20 years younger than that for invasive epithelial ovarian tumors

60% to 90% are stage I

Conservative surgery is possible in a high proportion of young patients

Literature Review of Pregnancies Following FSS for Tumors of Low Malignant Potential

Author No. Patients Stage No. Pregnancies

Lim-Tam 1988 35 IA-III 8

Gotlieb 1998 39 IA-III 22 in 15

Morris 2000 43 IA-III 25 in 12

Zanetta 2001 189 IA-III 44 in 44

Morris 2001 44 IA-III 17 in 14

Invasive Epithelial Cancer The majority of ovarian malignancies (95%)

10-20 % of ovarian cancers occur before the age of 40 years.

The 5-year survival of patients with Stage IA, grade 1, EOC treated conservatively is 90%

Conservative surgery may be performed in selected young patients with apparent disease confined to one ovary

Literature Review of Reproductive Function Following FSS for Invasive EOC

Author No. Patients Stage No.

Pregnancies No. Relapses

Colombo 1994 56 IA-IC 25 in 17 3

Zanetta 1997 56 IA-IC 27 in 20 5

Raspagliesi 1997 10 IA-III 3 in 3 0

Brown 1998 16 IA-IC 8 in 5 2

Morice 2001 25 IA-II 4 in 4 7

Schilder 2002 52 IA-IC 31 in 17 5

Kwon 2009 21 IA-IC 5 in 5 0

Low risk group Stage IA G1-2 literature review

Author No. Patients

Stage and Grade No. relapses No. Death

Zanetta 1997 30 IA G1-2 3 1Morice 2001 19 IA G1-2 3 3Schilder 2002 42 IA 4 2Morice 2005 27 IA G1-2 5 2Borgfeldt 2007 10 IA G1-2 0 0Park 2008 32 IA G1-2 1 0Schlaerth 2009 11 IA 1 1Anchezar 2009 11 IA G1 2 1Kajiyama 2010 30 IA 2 2Satoh 2010 108 IA G1-2 5 1Fruscio 2013 115 IA G1-2 9 3Ditto 2014 8 IA G1-2 2 0

High risk group Stage ≥ IAG3 literature review

Author No. Patients

Stage and Grade No. relapses No. Death

Raspagliesi 1997 10 > IA G1-2 0 0

Zanetta 1997 26 IA G3, IB, IC 2 2

Morice 2001 6 IC, II 4 NR

Schilder 2002 10 IC 1 0

Morice 2005 7 IA G3, IC,IIA 5 2

Borgfeldt 2007 1 IC G3 1 0

Park 2008 30 IA G3-IIIC 10 6

Schlaerth 2009 9 IC 2 2

Anchezar 2009 7 IC – IIIB 1 0

Kajiyama 2010 30 IB-IC 6 5

Satoh 2010 103 IA G3, IC 13 4

Fruscio 2013 125 IA G3-IIB 18 8

Ditto 2014 10 > IA G1-2 2 0

Sait et. al. Local Series A retrospective study of women conservatively treated for

primary ovarian cancer between January 2000 and December 2010 at King Abdulaziz University Hospital

39 patients 80% were stage I 52% were Germ cell tumor 8% patients had recurrent disease 20% had a normal pregnancy

Indications for FSS in ovarian cancer

Nonepithelial ovarian cancers

Ovarian tumors of low malignant potential

Early stage Epithelial ovarian carcinoma Stage IA G1-2

Future Perspectives The merged role of the treating physician as both life-save and

protector-of- future fertility has made the field of oncofertility a substantial part of gynecologic oncology nowadays

Prospectively designed and RCTs to evaluate safety of FSS are neither possible nor ethical

Our experience in outcomes after FSS mainly originates from retrospective case series

The gynecologic oncologist is in a unique position to provide young cancer patients with up-to-date fertility preservation information and fertility-sparing surgical alternatives

There is a need of close collaboration between cancer centers and reproductive centers in these cases

Conclusion After thorough insight of the current literature, FSS in

certain ovarian tumors appears a viable and safe option for women younger than 40 years who wish to preserve their childbearing potential

Only after thorough discussion and informed consent with careful balancing of the risks and benefits

The treating gynecologic oncologist should be fully aware of his double role in treating the malignant disease as well as in providing oncofertility care to young patients, by offering fertility-sparing alternatives when allowed so by tumor stage and histologic differentiation

Thank you